Does folic acid impact cancer risk?

There is convincing evidence that folate could play a modulatory role in cancer development, which may be positive or negative depending on the context. While adequate folate levels may be protective, too little may encourage cancer development, and too much may exacerbate preexisting cancer. The effect of supplemental folic acid on cancer risk has generally been found to be neutral, although research results have been mixed.

Folate is required for the maintenance, repair, and methylation of DNA, all of which serve preventative roles against cancer. Accordingly, a folate deficiency can lead to increased DNA breaks, mutations, and hypomethylation, which may increase cancer risk.^[1][2] Folate is also required for DNA synthesis and cell division, meaning that it could serve as a growth factor for preexisting cancerous or precancerous cells.^[1] Indeed, many cancer cells have increased expression of the membrane receptors responsible for folate uptake,^[3] and antifolate medications (e.g., methotrexate, pemetrexed), which block folate metabolism, are effective treatments for some cancers.^[4]

The vast majority of epidemiological research has shown that higher intakes of folate are associated with a reduced or unchanged risk of various types of cancer compared to lower intakes.^{[5][6][7][8][9][1][10]} Regarding supplemental folic acid, two meta-analyses of randomized controlled trials (RCTs) concluded that supplementation had no impact on the incidence of cancer in general or specific types of cancer.^[11][12][13] Contrary to this, another meta-analysis reported an increased risk of prostate cancer with supplementation.^[12] In 2023, the European Food Safety Authority (EFSA) expert panel stated that there was insufficient evidence to suggest a causal relationship between folic acid and the risk of prostate cancer or any other type of cancer.^[14]